Arrhythmias in Pulmonary Hypertension Assessed by Continuous Long-term Cardiac Monitoring (ASPIRE)

ArrhythmiaS in Pulmonary arterIal hypeRtEnsion and Right Heart Failure Assessed by Continuous Long-term Cardiac Monitoring

Arrhythmias are considered a prominent phenomenon in pulmonary hypertension (PH) as the disease progresses. According primarily to retrospective studies with up to 24 hours of monitoring, supraventricular tachycardias (SVT) can be found in 8-35% of patients, with significant impact on survival.

Furthermore, a few prospective studies to date deploying short-term monitoring (10 minutes-24 hours) have revealed lower heart rate variability (HRV) in patients with pulmonary arterial hypertension (PAH).

In ASPIRE arrhythmias and heart rate variability is being assessed via long term monitoring.

Currently the the loop-recorder is considered the gold standard for long-term continuous cardiac montoring. A non-invasive continuous monitoring could be of a great benefit for the patients, and could potentially contribute to treatment optimization.

The study will assess apple watches as a non-invasive tool compared to to the loop recorder, which is considered as the current gold standard.

Additionally, the study seeks to assess apple watches for monitoring as an independent wearable for risk assessment in PH.

Study Overview

• Status: Recruiting
• Conditions: Arrhythmias, Cardiac; Pulmonary Hypertension; Heart Rate Variability; Risk Assessment
• Intervention / Treatment: Device: Loop recorder implantation; Device: A smartwatch

Detailed Description

In general there is a lack of evidence of the arrhythmic burden in PH. The present study is the first to apply continuous long-term cardiac monitoring in patients with PH to describe the prevalence of arrhythmias in PH by continuous long-term cardiac monitoring. Furthermore, the correlation between heart rate variability and risk assessment parameters including WHO functional class (FC), NT-proBNP, 6MWT, cardiac parameters and cardiac function will be studies.

A few prospective studies have demonstrated lower HRV in PH than in healthy individuals, however only based on short-term monitoring (20 minutes to 24 hour) and only in a few patients. In retrospective studies, a higher mortality in children with PAH and low HRV has been shown with 24 hour Holter monitoring. Consequently, there is a lack of evidence regarding right heart failure and the prognostic value of HRV.

Risk assessment in PH is essential in the selection of treatment in PH and for prognosis in the study ASPIRE the investigators will assess the use of heart rate variability in pulmonary hypertension.

In conclusion the ASPIRE study will:

1. Assess the incidence and prevalence of arrhythmias using long term cardiac monitoring via a reveal LINQ loop recorder (Medtronic). Furthermore, the investigators will assess; Change in cardiac index, right atrial size, RV size, fibrosis and stroke volume.

2. The investigators will assess the arrhythmic burden in relation to:

   • Change in 6 MWT
   • Hemodynamic changes with RHC
   • Hemodynamic changes in echocardiography
   • The number of patients progressing one FC (Modified NYHA class)
   • Changes in NT-proBNP.
   • Hospital admission for any reason
   • Death or transplantation

3. Monitor heart rate variability and address a comparison to known risk markers and CMR and echocardiography.

   The study specifically seeks to investigate following:

   • The incidence and type of supraventricular and ventricular arrhythmias in PH by continuous long-term monitoring
   • The predictive value of both right and left ventricular cardiac magnetic resonance (CMR) imaging parameters for arrhythmogenesis in PAH, heart rate variability, and heart rate.
   • Optimization of specific therapy in PAH using continuous long-term arrhythmia monitoring
4. Monitor patients using smart watches (apple watches) to evaluate the applicability of long-term monitoring via apple watches in patients with pulmonary hypertension for irsk asessment.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Jørn Carlsen, MD, DMSc, FESC; Phone Number: (+45) 35458060; Email: joern.carlsen@regionh.dk
• Study Contact Backup: Name: Mads Andersen, MD; Phone Number: (+45) 21636430; Email: mads.oerbeak.andersen.01@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Department of Cardiology 2141 Copenhagen University Hospital, Rigshospitalet 9- Blegdamsvej
    • Contact: Jørn Carlsen, MD, DMSc; Phone Number: (+45) 35458060; Email: joern.carlsen@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Patients diagnosed with pulmonary hypertension:

Patients can be in WHO group 1 classified by one of the following subgroups:

• Idiopathic pulmonary arterial hypertension (IPAH)
• Heritable pulmonary arterial hypertension (HPAH)
• Drugs and toxins
• Associated with (APAH): specifically, connective tissue disease (CTD), HIV infection and congenital heart disease

Description

Inclusion Criteria:

• Pulmonary hypertension patients >18 years of age

  • Voluntary participation after giving informed verbal and written consent
  • Patients naïve to PAH-specific treatments
  • Patients on current PAH specific medication independent of duration of therapy
  • Patients can be in WHO group 1 classified by one of the following subgroups:
  • Idiopathic pulmonary arterial hypertension (IPAH)
  • Heritable pulmonary arterial hypertension (HPAH)
  • Drugs and toxins
  • Associated with (APAH): specifically, connective tissue disease (CTD), HIV infection and congenital heart disease
  • Patients with chronic thromboembolic pulmonary hypertension
  • Diagnosis of PAH confirmed by right heart catheterization
  • WHO/NYHA functional class II to IV symptoms
  • 6MWT distances of ≥50 meters and within 15% of each other on 2 consecutive tests preferably performed on different days during Screening.

Exclusion Criteria:

• Presence of 3 or more of the following risk factors for heart failure with preserved ejection fraction at Screening: BMI >30 kg/m2; diabetes mellitus of any type; systemic hypertension, significant coronary artery disease; or left atrial volume index (LAVi) >30 mL/m2.
• Evidence or history of left-sided heart disease and/or clinically significant cardiac disease.
• Acutely decompensated heart failure within 30 days prior to Screening
• Evidence of significant parenchymal lung disease
• Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (SBP) >160 mmHg or sitting diastolic blood pressure (DBP) >100 mmHg at Screening. • Systolic blood pressure >160 mmHg or < 90 mmHg; or diastolic blood pressure > 100 mgHg at Screening
• Male subjects with a corrected QT interval using Fridericia's formula (QTcF) >450 msec, and female subjects with QTcF >470 msec on ECG measured at Screening or Baseline.
• Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or that would confound study analysis or impair study participation or cooperation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence and prevalence of arrhythmias in pulmonary hypertension	Assessed throughout continuous cardiac monitoring	2022
Arrhythmias and their impact on heart function assessed with echocardiography	Change in function of the right and left heart chambers in the patients' with and without arrhythmias assessed with echocardiography.	2022
Heart rate variability and heart function assessed with CMR scans.	The patients' heart rate variability will be compared to the function of the right and left ventricle (LVEF, RVEF)	2022
Heart rate variability	Throughout continuous cardiac monitoring heart rate variability will be assessed as a clinical marker. It will be compared with already known clinical markers in pulmonary hypertension and compared with echocardiography and cardiac MR scans.	2023
Heart rate variability and chamber sizes assessed CMR scans	The patients' heart rate variability will be compared to the size of the right and left ventricle (ml)	2023
Change in heart function when having arrhythmias, assessed with CMR scans.	The patients' arrhythmic burden will be compared to the function of the right and left ventricle (LVEF, RVEF)	2023
Heart size in the group with and without arrhythmias, assessed with CMR scans.	The patients' arrhythmic burden will be compared to the size of the right and left ventricle (ml).	2023
Chamber sizes in patients with and without arrhythmias assessed with echocardiography.	Change in echocardiography parameters assess by the size of the right and left heart chambers (ml and cm2) in the patients with and without arrhythmias.	2023
The association between variables recorded via the apple watch and current risk assessment parameters in PH	Association models between the variables in order to assess the apple watch applicability for risk assessment.	2024

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arrhythmias and their impact on WHO functional class	Modified WHO functional class when having arrhythmias	2022

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arrhythmias and their impact on death or transplantation	Do any patients die because of the arrhythmias and will any patients need a transplantation because of terminal PH and arrhythmias.	2022
Arrhythmias impact on specific PAH therapy	How many patients will need escalation in PAH therapy when having arrhythmia and how much of an increase.	2022
Arrhythmias impact on six minute walking tests	Arrhythmias impact on reduction in number of meters performed in a six minute walking test during the study period.	2022
Arrhythmias and their impact on NT-proBNP	NT-proBNP change during the study period.	2022

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Actelion
• Investigators: Study Director: Jørn Carlsen, MD, DMSC, MD at Copenhagen University Hospital, Rigshospitalet 9- Blegdamsvej

Publications and helpful links

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Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2018
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: September 13, 2020
• First Posted (Actual): September 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Heart rate variability; Risk assessment; arrhythmias; Continuous heart monitoring via wearables
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Arrhythmias, Cardiac; Hypertension, Pulmonary
• Other Study ID Numbers: H-18005164

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes